Hostname: page-component-cd9895bd7-gbm5v Total loading time: 0 Render date: 2025-01-02T13:36:27.999Z Has data issue: false hasContentIssue false
  • English
  • Français

Cortical Glutaminase, β-Glucuronidase and Glucose Utilization in Alzheimer's Disease

Published online by Cambridge University Press:  18 September 2015

E.G. McGeer ,
P.L. McGeer ,
H. Akiyama  and
R. Harrop
E.G. McGeer*
Affiliation:
Kinsmen Laboratory of Neurological Research, Dept. of Psychiatry, University of B.C., Vancouver
P.L. McGeer
Affiliation:
Kinsmen Laboratory of Neurological Research, Dept. of Psychiatry, University of B.C., Vancouver
H. Akiyama
Affiliation:
Kinsmen Laboratory of Neurological Research, Dept. of Psychiatry, University of B.C., Vancouver
R. Harrop
Affiliation:
School of Computer Science, Burnaby, B.C.
*
Kinsmen Laboratory of Neurological Research, University of B.C., 2255 Westbrook Mall, Vancouver, B.C., Canada V6T 1W5
Rights & Permissions [Opens in a new window]

Abstract:

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

Large pyramidal neurons of rat and human neocortex stain immunohistochemically for phosphate-activated glutaminase (PAG). In a limited number of postmortem brains, we find large reductions in cortical PAG activity in Alzheimer's disease (AD). This finding is consistent with histological evidence that pyramidal neurons are affected in AD. The reductions are greater than those found in the same samples in choline acetyltransferase (ChAT) but the possible deleterious effects of coma and similar premortem factors on human PAG activity have yet to be assessed. The activity of (β-glucuronidase, a lysosomal enzyme which occurs in reactive astrocytes, is elevated in the same samples. Positron emission tomography (PET) studies, using 18F-fluorodeoxyglucose (FDG), have demonstrated significant deficiencies in glucose metabolism in the cortex in AD, with the parietal, temporal and some frontal areas being particularly affected. We found in serial scans of 13 AD cases, including one relatively young (44-46 year old) familial case, an exacerbation of the defect over time in most cases. We have found a negative correlation between the regional metabolic rates for glucose (LCMR(s)) measured premortem and the (β-glucuronidase activities measured postmortem on a few AD cases that have come to autopsy. The correlations between LCMR(s) and PAG and ChAT activities tend to be positive. The results are consistent with previous suggestions that decreased LCMR(s) in AD reflect local neuronal loss and gliosis.

Type
Research Article
Information
Canadian Journal of Neurological Sciences , Volume 16 , Issue S4 , November 1989 , pp. 511 - 515
Copyright
Copyright © Canadian Neurological Sciences Federation 1989

References

REFERENCES

1.Lewis, DA, Campbell, MS, Terry, RD, et al. Laminar and regional distribution of neurofibrillary tangles and neuritic plaques in Alzheimer’s disease: a quantitative study of visual and auditory cortices. J Neurosci 1987; 7: 1799–1808.CrossRefGoogle ScholarPubMed
2.Pearson, RCA, Esiri, MM, Hioms, RW, et al. Anatomical correlates of the distribution of pathological changes in the neocortex in Alzheimer’s disease. Proc Natl Acad Sci USA 1985; 82: 4531–4534.CrossRefGoogle Scholar
3.Rogers, J, Morrison, JH. Quantitative morphology and regional laminar distributions of senile plaques in Alzheimer’s disease. J Neurosci 1985; 5: 2801–2808.CrossRefGoogle ScholarPubMed
4.Conti, F, Rustioni, A, Petrusz, P, et al. Glutamat-positive neurons in the somatic sensory cortex of rats and monkeys. J Neurosci 1987; 7: 1887–1901.CrossRefGoogle ScholarPubMed
5.Storm-Mathisen, J, Leknes, AK, Bose, AT, et al. First visualization of glutamate and GABA in neurones by immunocytochemistry. Nature 1983; 301: 517–520.CrossRefGoogle ScholarPubMed
6.Rustioni, A, Cuenod, M. Selective retrograde transport of D-aspartate in spinal interneurons and cortical neurons of rats. Brain Res 1982; 236: 143–155.CrossRefGoogle ScholarPubMed
7.McGeer, PL, Eccles, JC, McGeer, EG. Molecular Neurobiology of the Mammalian Brain. New York; Raven Press, 1987: 180–186.Google Scholar
8.Donaghue, JP, Wenthold, RJ, Altschuler, RA. Localization of glutaminase-like and aspartate aminotransferase-like immunoreactivi-ties in neurons of cerebral cortex. J Neurosci 1985; 5: 2597–2608.CrossRefGoogle Scholar
9.Kaneko, T, Mizuno, N. Immunohistochemical study of glutaminasecontaining neurons in the cerebral cortex and thalamus of the rat. J Comp Neurol 1988; 267: 599–602.CrossRefGoogle ScholarPubMed
10.Akiyama, H, McGeer, PL, Itagaki, S, et al. Loss of glutaminase-positive cortical neurons in Alzheimer’s disease. Neurocheni Res 1989; 14: 453–458.Google ScholarPubMed
11.Altshuler, RA, Monaghan, DT, Haser, WG, et al. Imniunocytochemical localization of glutaminase-like and aspartate aminotransferase-like immunoreactivities in the rat and guinea pig hippocampus. Brain Res 1985; 330: 225–233.CrossRefGoogle Scholar
12.Cross, AJ, Crow, TJ, Dawson, JM, et al. Subcellular pathology of human neurodegenerative disorders: Alzheimer-type dementia and Huntington’s disease. J Neurochem 1986; 47: 882–889.CrossRefGoogle ScholarPubMed
13.McGeer, PL, Kamo, H, Harrop, R, et al. Comparison of PET, MRI and CT with pathology in a proven case of Alzheimer’s disease. Neurology 1986; 36: 1569–1574.CrossRefGoogle Scholar
14.Kaneko, T, Urade, Y, Watanabe, Yet al. Production, characterization and immunohistochemical application of monoclonal antibodies to glutaminase purified from rat brain. J Neurosci 1987; 7: 302–309.CrossRefGoogle ScholarPubMed
15.McGeer, EG, Singh, EA, McGeer, PL. —Glutamyl transferase: normal cortical levels in Alzheimer’s disease. Alz Dis Assoc Disord 1987; 1: 50–63.CrossRefGoogle Scholar
16.Lowry, OH, Rosebrough, NJ, Farr, AL, et al. Protein measurement with the Folin phenol reagent. J Biol Chem 1951; 193: 265–275.CrossRefGoogle ScholarPubMed
17.McGeer, PL, Kamo, H, Harrop, R, et al. Positron emission tomography in patients with clinically diagnosed Alzheimer’s disease. Can Med Assoc J 1986; 134: 597–607.Google ScholarPubMed
18.Akiyama, H, Harrop, R, McGeer, PL, et al. Crossed cerebellar and uncrossed basal ganglia and thalamic diaschisis in Alzheimer’s disease. Neurology 1989; 39: 541–548.CrossRefGoogle ScholarPubMed
19.McGeer, PL. Brain imaging in Alzheimer’s disease. Br Med Bull 1986; 42: 24–28.Google ScholarPubMed
20.McGeer, PL, Itagaki, S, Tago, H, et al. Reactive microglia in patients with senile dementia of the Alzheimer type are positive for the histocompatibility protein HLA–DR. Neurosci Lett 1087; 79: 195–200.CrossRefGoogle Scholar
21.Itagaki, S, McGeer, PL, Akiyama, H. Presence of T-cytotoxic suppressor and leucocyte common antigen positive cells in Alzheimer’s disease brain tissue. Neurosci Lett 1988; 91: 259–264.CrossRefGoogle ScholarPubMed
22.Procter, AW, Lowe, SL, Palmer, AM, et al. Topographical distribution of neurochemical changes in Alzheimer’s disease. J Neurol Sci 1988; 84: 125–140.CrossRefGoogle ScholarPubMed
23.Francis, FT, Bowen, DM. Tacrine, a drug with therapeutic potential for dementia: post-mortem biochemical evidence. Can J Neurol Sci (in press - this symposium).Google Scholar
24.McGeer, PL, McGeer, EG. Enzymes associated with the metabolism of catecholamines, acetylcholine and GABA in human controls and patients with Parkinson’s disease and Huntington’s chorea. J Neurochem 1976; 26: 65–76.CrossRefGoogle Scholar